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SummaryBackgroundTapentadol is a mu‐opioid receptor agonist and norepinephrine reuptake inhibitor. In clinical trials, tapentadol provided somatic pain relief comparable to mu‐opioids such as oxycodone, with significantly less gastrointestinal adverse effects. The acute effects of tapentadol on gastrointestinal and colonic transit are unclear.AimTo compare acute effects of oral tapentadol and oxycodone on gastric, small bowel and colonic transit of solids in 38 healthy human subjects.MethodsIn a randomised, parallel‐group, double‐blind, placebo‐controlled study of the effects of identical‐appearing tapentadol immediate release (IR), 75 mg t.d.s., or oxycodone IR, 5 mg t.d.s., for 48 h, we measured gastric (GE), small bowel (SBT measured as colonic filling at 6 h) and colonic transit by validated scintigraphy. Drug was commenced on the evening before the start of the transit test. The primary endpoints were overall colonic transit (geometric centre, GC) at 24 h and GE half‐time (t1/2). ancova of transit data included gender or BMI as covariates. Adverse effects were summarised.ResultsAt the doses tested, oxycodone and tapentadol significantly delayed GE t1/2 and SBT, but not overall colonic transit, compared to placebo. Transit profiles in all regions were not significantly different between oxycodone and tapentadol at the doses tested. Both oxycodone and tapentadol were associated with nausea and central effects attributable to central opiate effects.ConclusionsTapentadol significantly delayed gastric emptying t1/2 and small bowel transit, similar to oxycodone. These data suggest that acute administration of tapentadol may not have significant advantages over standard mu‐opioids, in terms of the potential to avoid upper gastrointestinal motor dysfunction.

Purpose Trastuzumab is a humanized monoclonal antibody against the human epidermal growth factor receptor 2 (HER2). The clinical benefits of adjuvant trastuzumab have been demonstrated in interim analyses of four large trials. Initial data of the combined analysis of the North Central Cancer Treatment Group (NCCTG) N9831 Intergroup trial and National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31 trial were reported in 2005. Long-term follow-up results on disease-free survival (DFS) and overall survival (OS) have been awaited. Patients and Methods Patients with HER2-positive operable breast cancer were randomly assigned to doxorubicin plus cyclophosphamide followed by paclitaxel with or without trastuzumab in the NCCTG N9831 and NSABP B-31 trials. The similar design of both trials allowed data from the control and trastuzumab-containing arms to be combined in a joint analysis. Results At 3.9 years of median follow-up, there continues to be a highly statistically significant reduction in DFS event rate in favor of the trastuzumab-containing arm (P < .001). Similarly, there continues to be a statistically significant 39% reduction in death rate in favor of the trastuzumab-containing arm (P < .001). Conclusion These data demonstrate consistent DFS and OS advantages of adjuvant trastuzumab over time, with the longest follow-up reported to date. The clinical benefits continue to outweigh the risks of adverse effects.

Abstract Abstract #75 Background: The primary aims of this study were to determine 1) if a concurrent regimen of therapy containing cyclophosphamide compared to a sequential regimen containing cyclophosphamide would prolong disease-free survival (DFS) and overall survival (OS) and 2) if a regimen without cyclophosphamide was at least as efficacious as the two regimens containing cyclophosphamide. The secondary aims were to compare toxicities among the three regimens and to compare differences in amenorrhea in premenopausal women in each arm and its relationship to outcome.&#x2028; Materials and Methods: 5351 pts with cT1-3, N0-1, M0 were enrolled from 3/1/99 to 3/31/2004. 1783 pts were randomized to Group 1 [doxorubicin (A) 60 mg/m2 and C 600 mg/m2 q 3 weeks (wks) x 4 followed by docetaxel (T) 100 mg/m2 q 3 wks x 4], 1784 pts to Group 2 [A 50 mg/m2 and T 75 mg/m2 q 3 wks x 4], and 1784 to Group 3 [A 50 mg/m2 T 75 mg/m2 and cyclophosphamide (C) 500 mg/m2 q 3 wks x 4]. All patients with ER-positive tumors received hormonal therapy after completing chemotherapy. The protocol specifies that 800 deaths are required for the definitive analysis. This is expected to occur by Fall 2008.&#x2028; Results: Mean time on study is currently 79 months. At entry, 46% of pts were &lt; 49 yrs; 54% were &gt; 50 yrs. 82% were white, 10% black, 4% Hispanic. 66% had 1-3 positive nodes, 26% had 4-9, and 8% had 10+. 75% of pts were ER pos. 49% had lumpectomy, 51% mastectomy, and 24% local/regional radiotherapy. Mean tumor size was 2.5 cm. The presentation will include the first results of DFS, OS, and relevant toxicities from the trial. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 75.